Defibrotide treatment for the prevention of organ rejection and injury

Abstract

The present disclosure provides methods of preventing, lessening the effects, or treating organ injury and/or organ rejection optionally associated with organ transplant comprising administering defibrotide. The defibrotide can be administered to the donor organ via the donor organ's artery, to the donor organ via a preservation bath, or to the patient.

1 . A method of preventing and/or lessening the effects of and/or treating organ injury and/or organ rejection in a patient comprising administering a therapeutically effective amount of defibrotide. 
     
     
         2 . The method of  claim 1 , wherein the patient is receiving or about to receive or has received transplant of a donor organ or donor tissue. 
     
     
         3 . The method of  claim 2 , wherein the donor organ is selected from the group consisting of a heart, heart valve, stomach, testis, liver, lungs, kidneys, pancreas, uterus, intestine, bladder, composite tissue, xenograft, and thymus, and/or wherein the donor tissue is selected from the group consisting of bones, bone marrow, tendons, corneae, skin, valves, nerves, and veins. 
     
     
         4 . The method of  claim 2 , wherein defibrotide is administered to the patient, to the donor organ intravenously via an artery, or to a preservation bath that is used to store the organ for transfer. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The method  claim 1 , wherein the defibrotide is administered before the development of organ injury and/or organ rejection. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein defibrotide is administered to the patient once or four times per day. 
     
     
         10 . The method of  claim 1 , wherein defibrotide is administered to the patient in multiple doses per day. 
     
     
         11 . The method of  claim 1 , wherein defibrotide is administered in two to ten doses per day. 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein an initial dose of defibrotide is administered to the patient about 6 hours after transplant of a donor organ. 
     
     
         14 . The method of  claim 1 , wherein the defibrotide is administered at a dose between 1 mg/kg and 10 mg/kg. 
     
     
         15 . The method of  claim 14 , wherein the defibrotide is administered at a dose of 2.5 mg/kg or 6.25 mg/kg. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the defibrotide is administered intravenously or subcutaneously. 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein defibrotide is administered intravenously, every six hours at a dose of 2.5 mg/kg or 6.25 mg/kg. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the defibrotide is administered to the donor organ intravenously via an artery at a dose of 2.5 mg/kg or 6.25 mg/kg, or to a preservation bath that is used to store the organ for transfer at a dose of 2.5 mg/kg or 6.25 mg/kg. 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein the defibrotide is a high concentration defibrotide formulation. 
     
     
         24 . The method of  claim 23 , wherein the high concentration defibrotide formulation is formulated for subcutaneous delivery or intravenous delivery. 
     
     
         25 . The method of  claim 23 , wherein the high concentration defibrotide formulation comprises about 160-200 mg/mL of defibrotide and about 20 mM glycylglycine, and is formulated for subcutaneous delivery to a patient. 
     
     
         26 . The method of  claim 23 , wherein the high concentration defibrotide formulation further comprises between about 10 mM to about 34 mM sodium citrate. 
     
     
         27 . The method of  claim 23 , wherein the high concentration defibrotide formulation comprises about 160-200 mg/mL of defibrotide, about 20 mM glycylglycine, and about 10-25 mM sodium citrate, wherein the formulation is formulated for subcutaneous or intravenous delivery to a patient. 
     
     
         28 . The method of  claim 1 , wherein the organ injury is selected from the group consisting of interstitial fibrosis, tubular atrophy, glomerulosclerosis, acute kidney injury, diffuse alveolar damage, nonalcoholic steatohepatitis, fibrosis, cardiac allograph vasculopathy, and ischemia reperfusion injury (IRI).